Preparation of 1-(carbamoyl)-n-(carbamoyloxy)thio-formimidates from alkyl acetoacetates

ABSTRACT

1-(CARBAMOYL-N-(CARBAMOYLOXY)THIOFORMIMIDATES SUCH AS METHYL 1-(CARBAMOYL)-N-(METHYLCARBAMOLOXY) THIOFORMIMIDATE AND METHYL 1-DIMETHYLCARBAMOYL)-N(METHYLCARBAMOYLOXY)THIOFORMIMIDATE ARE PREPARED BY THE STEPS OF (A) CHLORINATING AN ALKYL ACETOACETATE IN THE PRESENCE OR ABSENCE OF A SOLVENT SUCH AS WATER OR AN ALCOHOL; (B) REACTING THE PRODUCE OF (A) WITH AN ALKYL NITRITE IN WATER OR AN ALCOHOL AT -20 TO 50*C.; (C) MIXING THE HYDROXAMOYL CHLORIDE FORMED IN (B) WITH AN ALKYL MERCAPTAN AND THEN ADDING A BASE; (D) REACTING THE PRODUCT OF (C) WITH 2 MOLES OF AMMONIA OR AN AMINE IN THE PRESENCE OF WATER OR AN ALCOHOL; AND (E) REACTING THE PRODUCT OF (D) WITH EITHER (1) A CARBAMOYL CHLORIDE, IN THE PRESENCE OF A BASE; OR (2) AN ISOCYANATE, OPTIONALLY IN THE PRESENCE OF A BASIC CATALYST; IN WATER OR ORGANIC SOLVENTS SUCH AS ACETONE AND METHYLENE CHLORIDE.

ited States Patent Offic 3,557,190 Patented Jan. 19, 1971 US. Cl. 26048219 Claims ABSTRACT OF THE DISCLOSURE 1 (carbamoyl)N-(carbamoyloxy)thioformimidates such as methyll-(carbamoyl)-N-(methylcarbamoyloxy) thioformimidate and methyl 1dimethylcarbamoyl)-N- (methylcarbamoyloxy)thioformimidate are preparedby the steps of (a) chlorinating an alkyl acetoacetate in the presenceor absence of a solvent such as water or an alcohol;

(b) reacting the produce of (a) with an alkyl nitrite in water or analcohol at 20 to 50 C.;

(c) mixing the hydroxamoyl chloride formed in (b) with an alkylmercaptan and then adding a base;

(d) reacting the product of (c) with 2 moles of ammonia or an amine inthe presence of Water or an alcohol; and

(e) reacting the product of (d) with either (1) a carbamoyl chloride, inthe presence of a base; or (2) an isocyanate, optionally in the presenceof a basic catalyst; in Water or organic solvents such as acetone andmethylene chloride.

BACKGROUND OF THE INVENTION This invention relates to methods forpreparing l-(carbamoyl)-N-(carbamoyloxy)thioformimidates. Moreparticularly, this invention is directed to methods of preparing thethioformimidates by chlorinating an alkyl actoacetate, reacting theproduct with an alkyl nitrate, reacting the resulting hydroxamoylchloride with an alkyl mercaptan in the presence of a base, thenaminating, and then preparing the desired thioformimidates by reactionWith either a suitable carbamoyl chloride in the presence of a base or asuitable isocyanate usually in the presence of a basic catalyst.

The product thioformimidates are useful as pesticides and can beprepared in the manner disclosed in copending application Ser. No.728,739, filed May 13, 1968. They can also be prepared from glyoxylicacid in the manner disclosed and claimed in copending application Ser.No. 772,811, filed Nov. 1, 1968.

While it has been known in the art that chlorinations such as step (a)were feasible, see I. Am. Chem. Soc., 61, 892 (1939), and that alkylchloroacetoacetates could be oximated, see G. Hesse and G. Krehbiel,Ber., 88, 130 (1955), such reactions resulted in poor product yields(less than 60% and involved the use of ethyl ether as a solventsaturated with hydrogen chloride. By the methods of this invention it ispossible to carry out these steps without the use of ethyl eher which isboth hazardous and inconvenient, with the use of only small amounts ofhydrogen chloride, and with much improved yields (greater than 80%).Moreover, by the methods of this invention it is possible to prepare thethioformimidates of Formula 1 below in a five-step process in which thefirst four steps can be operatively combined. By thus avoiding thenecessity to separate and recover intermediate compounds the methods ofthis invention permit economic preparation of the compound of Formula 1below in outstanding yield.

SUMMARY This invention is directed to the preparation ofl-(carbamoyl)-N-(carbamoyloxy)thioformimidates of the fol lowing formulawherein R is alkyl of 1 through 4 carbon atoms or alkenyl of 3 through 4carbon atoms;

R is hydrogen, alkyl of 1 through 4 carbon atoms, alkenyl of 3 through 4carbon atoms, methoxy, or cycloalkyl of 3 through 5 carbon atoms;

R is hydrogen, alkyl of 1 through 4 carbon atoms or alkenyl of 3 through4 carbon atoms; with the proviso that R and R can be joined and arealkylene of 2 through 6 carbon atoms, and with the limitation that R andR never total more than 7 carbon atoms;

R; is alkyl of 1 through 3 carbon atoms, allyl or propargyl; and

R is hydrogen or methyl;

by the steps comprising:

(a) Chlorinating an alkyl acetoacetate in the presence or absence ofwater, methanol, ethanol, isopropanol or their mixtures at a temperaturebetween 0 C. and 70 C.;

(b) Reacting the product of (a) with an alkyl nitrite in the presence ofhydrogen chloride, and in the presence of water, methanol, ethanol,isopropanol or their mixtures at a temperature between 20 C. and 50 C.;

(c) Mixing the product of (b) with an alkyl mercaptan, then adding baseto the reaction mixture;

(d) Aminating the product of (c) with 2 moles of ammonia or an amine inthe presence of water or alcohol; and

(e) Reacting the product of (d) with either (1) carbamoyl chloride inthe presence of a base; or (2) an isocyanate in the presence or absenceof a basic catalyst; in water, acetone, methylene chloride, methyl ethylketone, or methyl isobutyl ketone.

The compounds of Formula 1 and their use as pesticides are described andexemplified in application Ser. No. 728,739, referred to above.

DESCRIPTION OF THE INVENTION The process of this invention used inpreparing the compounds of Formula 1 comprises the five steps enumeratedabove, and more fully described as follows:

Step (a): The formation of an alkyl 2-chloroacetoacetate by chlorinationof an alkyl acetoacetate is represented by the following equation:

wherein R is methyl, ethyl or isopropyl.

The chlorination can be carried out with chlorine, an alkalihypochlorite, or sulfuryl chloride, with the latter the preferredchlorinating agent in the absence of solvent. It can also be carried outin the presence of solvents such as water, methanol, ethanol,isopropanol and their mixtures, and when water is used elementalchlorine is the preferred chlorinating agent. When solvents are used theconcentration of the acetoacetic ester will ordinarily range betweenabout 10 and 50% by weight. Of the acetoacetates the ethyl ester is thepreferred starting material.

The alkyl acetoacetate is ordinarily charged to the reaction vesselalong with a solvent if one is used. The chlorinating agent is thenadded gradually in an amount ranging from about stoichiometric to anexcess of about 5%. The temperature range during chlorination is aboutto 70 C. and for convenience and economy is preferably kept betweenabout 20 and 50 C.

After addition of the chlorinating agent is complete, the reactionmixture is heated at about 50 C. for a short period of time to completethe reaction. The product can then be recovered and purified or the step(b) reaction can be carried out without isolating the alkylchloroacetoacetate.

Step (b): Step (b) comprises formation of the hydroxamoyl chloride andis illustrated by the equation 0 Cl 0 O NOlI II I H IVOII II II 1to-Cou-0oir3 RONU lt0-()(,C1O+

Clh Olt wherein R is as defined in step (a), R is methyl, ethyl orisopropyl and R" is hydrogen, methyl, ethyl or isopropyl.

If the product of step (a) has been prepared in the absence of asolvent, solvent is added prior to the reaction of step (b) in an amountsufficient to give a concentration of alkyl Z-chloroacetoacetate of fromabout to 50% by weight.

Suitable alkyl nitrites can be prepared by methods known to the art suchas disclosed in Organic Synthesis, Vol. II, page 204, page 363.Preferred nitrites are the methyl and ethyl nitrites, which can begenerated and fed simultaneously to the reaction mixture at a desiredrate. Alternatively, the nitrites can be prepared and condensed bychilling and then be vaporized when used in reaction (b).

The nitrosation is ordinarily carried out at a temperature between aboutC. and 50 C., and preferably between 0 C. and 10 C. The amount ofnitrite used will range from about stoichiometric to a slight excessbased on the product of step (a). The nitrite is usually added over aperiod of about an hour and after addition is complete the mixture isstirred while the temperature gradually rises to about C. The holdperiod is usually several hours with four hours not unusual.

The reaction of step (b) is catalyzed by the presence of small amountsof hydrogen chloride. Ordinarily l to 2% by Weight of hydrogen chloridebased on the weight of chloroacetoacetic ester is sufiicient. Ifhydrogen chloride is used to generate the nitrite used, SUlTlClfil'lthydrogen chloride is present in the nitrite to catalyze the reaction ofstep (b).

Suitable solvents include water. methanol, ethanol, isopropanol andtheir mixtures, with the alcohols preferred and ethanol most preferredas a solvent. The product of step (b) can be isolated by filtration,extraction or evaporation of solvent but it is preferred to go directlyto step (c) without isolating the product of step (b).

Step (c): The hydroxamoyl chloride from step (b) is mixed with an alkylmercaptan in a solvent and then the pH is raised by addition of a baseaccording to the equation wherein R, R" and R are as defined above.

For best yields the reaction product of step (b) is cooled to below 20C. prior to addition of the mercaptan. A temperature range of 0 to 10 C.is most preferred.

Bases suitable for adjusting the pH are the hydroxides, carbonates andbicarbonates of sodium, potassium, calcium and magnesium. The final pHshould be between 5 and 9 and a pH of about 7 is preferred.

The product can be isolated if desired by conventional techniques suchas filtration or solvent extraction. Alternatively, the product mixturecan be used as in step (d).

Step ((1): The product of step (c) is reacted with an amine in thepresence of water, methanol, ethanol, isopropanol or their mixturesaccording to the equation wherein R, R, R R and R areas defined above.

If the product of step (c) was isolated it is first dispersed withstirring in the solvent medium, preferably in one of the alcohols or analcohol-water mixture.

To this mixture is added approximately 2 moles of ammonia, or a primaryor secondary amine. A tertiary amine such as trimethylamine can besubstituted for one mole of these amines with about the same result. Twomoles of amine are necessary because one mole forms a salt with theoxime function while another mole participates directly in the reaction.

The product of step (d) can be isolated in a conventional manner such asby filtration or evaporation of the solvent. It is desirable to isolatethis product or at least to remove any excess ammonia or amine, prior toperforming the reaction of step (e).

Step (e): Conversion of the product of step (d) to the oxime carbamateis carried out by reacting the product NO II wherein R R R R and R areas defined above. The reactions of step (e) are carried out in a solventsuch as water, acetone, methyl ethyl ketone, methyl isobutyl ketone, ormethylene chloride, at a temperature which can range from below 10 C. tothe boiling point of the solvent. Use of anhydrous solvents ispreferred. The reaction of step (e is facilitated by the presence of abasic catalyst such as trimethylamine or triethylenediamine. Thereaction of step (e is carried out in the presence of a base such astriethylamine, trimethylamine or the hydroxides, carbonates orbicarbonates of sodium, potassium, calcium or magnesium.

Alternatively, the sodium salt of the product of step (d) can be formedby reation with a metal hydride such as sodium hydride. The resultingsodium salt can then be reacted with a carbamoyl chloride in an inertsolvent such as tetrahydrofuran to obtain products as obtained in the (ereaction.

The 1 (carbamoyl) N (carbamoyloxy)thioformidate products of step (e) canbe isolated by conventional procedures such as filtration or extraction.

Of the steps (a) through (c) the most important is step (b) whichprovides an advantageous method of preparing the hydroxamoyl chloride.One preferred sequence of reation is to chlorinate in step (a) in theabsence of a solvent and operatively combine steps (a) through (d),carrying out steps (b), (c) and (d) in an alcohol or water.

The process of this invention is further illustrated in product isdissolved in 200 parts of methanol and 100 the following exampleswherein parts and percentages parts of anhydrous dimethylamine is addedbelow 30 C. are by weight unless otherwise noted. The mixture is thenallowed to stand at ambient tem- EXAMPLE I peratures for several hours.Removal of solvent and excess amine under reduced pressure yields 101parts of methyl 1 (dimethylcarbamoyl) N hydroxythioformi- To 130.1 partsof ethyl acetoacetate is added 141.7

parts of sulfuryl chloride over about one hour at 30-35 id m C. Afteraddition is complete the reaction mixture is held T a suspensicn of 70parts of methyl l-(dimethylcarbat 50 C. for 30 minutes, and then brieflysparged with amoyl) N hydroxythioformimidate and /2 part of trinitrogen.10 ethylenediamine in 350 parts of acetone at 4 C. is

To the resulting ethyl 2-chloroacetoacetate is added dd d l l 27 parts fmethyl isocyanate, Th t m- 394 Parts of ethanol- In Separatfl Vessel 200P of perature of the reaction mass rises to 58 C. during the 36%hydrochloric acid is added to 145 parts of sodlum addition. After thetemperature of the reaction mass has n1tr1te and 104 parts of ethanol in100 parts of Water. subsided to 25 C., the solvent is evaporated underre- The ethyl nitrite evolved 1s collected In a hlll d trap 15 ducedpressure, and the resulting residue crystallized. Re- To the ethanoliesolution of ethyl 2-chloroaceotacetate crystallization from benzenegives an isomer of methyl is added 75 parts of ethyl nitrite 1n one hourat 5 C. The 1 (dimethylcarbamoyl) N (methylcarbamoyloxy)- reactionmixture is stirred at 5 C. for a further four thioforrnimidate, meltingpoint 109-110 C. Recrystalhc-urs and then allowed to rise slowly toambient temlization from water gives the other isomer of methylperature. 20 1 dimethylcarbamoyl) N (methylcarbam0yloxy)- The reactionmixture, which contains l-ethoxycarbonthioformimidate, melting point101103 C. ylformhydroxamoyl chloride, is then cooled to C. Similarresults are obtained in the above example by and 60 Parts of methylmefcaptan added, followed y substituting equivalent amounts of methylacetoacetate the gradual addition of about 160 parts of 50% aqueous orisopropyl acetoacetate for the ethyl acetoacetate. Likesodium hydroxldesolution at 10 to -5 C., so that 5 wise equivalent quantities of methylnitrite or isopropyl a stable pH of 7 is obtained. Most of the solvent1s renitrite can be substituted for the ethyl nitrite in EX- moved underreduced pressure. The residue is mixed ample I with 400 parts of waterand extracted with dichlorometh- The compounds of Table I are preparedby the proane. After evaporation of the dichloromethane under reedure ofExample I, using the mercaptans, amines and duced pressure, a residue ofcrude methyl l-ethoxyisocyanates listed in place of the methylmercaptan, dicarbonyl N hydroxythiformimidate is obtained. Thismethylamine and methyl isocyanate of Example I.

TABLE I 1\lercaptan Amine Isoeyanate Product Ethyl mercaptau lDimethylamine Methyl isoeyanate Elhyh l gilnethylcarbamoyl-N-(methylcarbamoyloxy)thio ormum a 8. Allylmercaptan dodo Allyl l-dimethylcarbamoyl-N-(methylcarbamoyloxy)thielormimidate.But-2-enyl mercaptan do Ethyl isocyanate Blflt-irenylildimethylcarbamoyl-N-(ethylcarbamoyloxy)thi- 01'11111'111 a G. Isopropylmercaptan do Allyl isocyanate lst propyldliimethylcarbamoyl-N-(allylcarbamoyloxy)thloormlml a 8. Methylmercaptan do Propargyl isoeyanate Methyll-dimethylcarbamoyl-N-(propargylearbamoyloxy) thioformimidate. Iropylmercaptan" Methyl is0cyanate. Piiopyl lgliriethylcarbamoyl-N-(methylcarbamoyloxy)thio- Ol'mll'l'll a e. Allylmorcaptan Allyl isocyanate.-. Allyllidlmethylcarbamoyl-N-(allylcarbamoyloxy)thiolormlml a 6.Isopropylmercaptan do Methyl isocyanata Isopropyll-dimethylcarbarnoyl-N-(methylcarbamoyloxy) thioformimidate.Butylmereaptan -d0 do Butyl ldimethylcarbamoyl-N-(methylcarbamoyloxy)thioformimidate.sec-Butylmercaptan do do sec-Butyl1-dimethy1carbamoyl-N-(methylcarbamoyloxy) formimidate.tert-Butylmercaptan do do tert-Butyl 1-imethy1carbamoylN-(methylcarbamoyloxy) thioiormimidate. Methyl mercaptando Ethyl isoeyanate Methyl lgirtnethylcarbamoybN-(ethylcarbamoyloxy)thioormlml a e. Butylmercaptando do Butyl (l-tlimethylcarbamoyl-N-(ethylcarbamoyloxy)thioformum at e.Methyl meroaptan do Is0pr0py1is0cyanate... Methyll-dimethylcarbamoyl-N-(isopropylcarbamoyloxy) thioformimidate.Butylmercaptan do do Butyll-dimethylcarbamoyl-N-(isopropylcarbamoyloxy)thioformixnidate.Allylmercaptan do Propyl isocyanate Allylldlmethylcarbamoyl-N-(propylcarbamoyloxy)thiofor- Il'llml 2L 8. Methylmercaptan do Allyl isocyanateMethyldl-limethylcarbamoyl-N-(allylcarbamoyloxy)thiofor- 11111111 a 8.Butylmercaptan do do Butyldlkdimethylcarbamoyl-N-(allylcarbamoyloxy)thiotormlml a e. Allylmercaptan do Propargyl isocyanate Allyl l-digrirelhylcarbamoyl-N-(propargylcarbamoyloxy)thic- OIIIllIIll a e.Methyl morcaptan Methylamine Methyl isocyanate Methyl 1-nlethy1earbamoyD-N-(methylearbamoyloxy)thio- 0111111111 8, '3. DoButylamine do Metliyltl-gbiltylcarbamoyl)-N-(methylcarbamoyloxy)thlolor-Inlml a e. Isopropylmercaptan Oyclopropylamine do Isopropyl1-(eyclopropylcarbamoyl)-N-(methylcarbamoyloxy)thioformimidate. Allylmereaptan N,O-dimethylhydroxylamine Ethyl isoeyanate Allyl 1-(Nmethoxy-N-methylcarbamoyl)-N-(ethylcarbmnoyloxy)th1oformimidate. Butylmercaptan Allylamine do Butyl lfiallylcarbamoyl)-N-(ethylearbamoyloxythiofor- Il'lll'nl a 9. Methyl melcaptal'l Diallylamine Allyl isocyanateMethyld l-(diallylcarbamoyl)-N-(allylcarbamoyloxy)thiotor- 11111111 218. Ethyl mercaptan Isopropylamine do Elhyll-tgogwopylcarbamoylyN-(a1lylcarbam0yl0xy)thio- 01111111'11 a e. Methylmercaptan Ethylamine Propargyl is0cyanate Methyll-%tl1ylcarbamoyl)-N-(propargylcarbamoyloxy)thio- ()lmll'l'll a 6- DoDiethylamine Methyl isoeyanate Methyl 1-dlethylcarbamoyl)-N-(methylcarbamoyloxy)thio- Olmlml a 9. DoDiisopropylamlne do Methyl1-(diisopropylcarbamoyl)-N-(methylcarbamoyl0xy) thioformimidate. Ethylmercaptan But-2-enylamide Isopropy1is0cyanate. Ethyl 1-(but-2enylearbamoyl)-N-isopropylcarbamoyloxy) thioformimidate.

Crude methyl 1 ethoxycarbonyl N hydroxythioformimidate obtained as inExample I above, is dissolved in 200 parts of concentrated aqueousammonia at a tem- TABLE I.Continned Mercaptau Amine Isoeyanate ProductMethyl mercaptan Aziridino Methyl isoeyanate Methyll-aziridinocarbonyl)N-(methylcarbamoyloxy)thiofoi'rnirni ate. DIlexahydroazepine d0 Methyl1-(hexahydroazepinoearbonyD-N-(methylcarbamoyl- 0xy)thi0formimidate. DoPyrrohdine do Methyl 1-(pyrrolidinoearbonyl)N-(methylearbamoyloxy)thioformimidate. D0 Methylamlne Allyl isocyanateMethyld1-(methylearbamoyD-N-(allylcarbamoyloxy)thioformimi ate. ])0Allylamine Iropargylisoeyaneta... Methyl1-(allylearbarnoyD-N-(propargylcarbalnoyloxy)thio formimidate. l)0N,Odimethyll1ydroxylamine Methyl isouyanate Methyl1-(N-methoxy-N-methylcarbamoyl)N-(methylcarbamoyloxy)thiofol'mlmidate.D0 Nmethyl-N-ethylamlne Allyl isocyanate Methyl1-(N-methyl-N-ethylearbamoyl)N-(allylearbamoyloxy)thiolormimidate. Ethylmercaptan Piperidine .do Ethyl-(piperidinocarbonyl)N-(allylcarhamoyloxy)thioiormimi ate. Do .d0 Butylisoeyanate Ethyll-(piperidinoearbonyl)N-(butylcarbamoyloxy)thioformirnldate. Butylmercaptan ..d0 Methyl isocyanate Bptyll-(giperidinocarbonyl)N-(methylearbamoyloxy)thioormimi ate. Do do Butylis0eyanate Butyl1-(piperidinoearbonyl)-N-(butylearbamoyloxy)thioformilnidate. Methylmereaptan N-methyl-N-butylamlne Methyl isoeyanate Methyll-(N-methyl-N-butylcarbamoyl)N-(methylcarbamoyloxy)thioformimidate. D0N-methyl-N-allylaminc ..d0 Methyl1-(N-methyl-N-allylcarbamoyl)-N-(methylcarhalnoyloxy)thioformimidatc.

EXAMPLE II EXAMPLE III To a solution of 164.6 parts of distilled ethyl2-chloroacetoacetate in 394 parts of ethanol is added 77 parts of ethylnitrite, prepared as described in Example I, in one perature below 30 C.The solution is allowed to stand 45 hour at 5 C. The reaction mixture isstirred at 5 C. for overnight. After removal of a small amount of undisafurther four hours and then allowed to rise slowly to solved material byfiltration, the filtrate is concentrated ambient temperature. Thereaction mixture is then cooled under reduced pressure to give 105 partsof methyl lto C., and 60 parts of methyl mercaptan is added,(carbamoyl)N-hydroxythiotormimidate, melting point followed by thegradual addition of about 80 parts of 50% 163-164 C. aqueous sodiumhydroxide solution at -10 to 5 C.,

To a Suspension of 0 parts f methyl 1 (carbam0y1) so that a stable pH of7 is obtained. Most of the solvent N hydroxythioformimidate and 1 partof triethy1enedi IS I'CHIOVECI under reduced pressure. The res1due ismixed amine in 2000 parts of acetone at 40 C. is added slowly Wlth 400Parts of Wate'r and extrffwted With dlchlofo' 171 parts of methylisocyanam The temperature; of the methane. After evaporation of thedichloromethane under reaction mixture rises to 58 C. during theaddition and reduced Pressure, I P P P Crude methyl fY then subsides to25 C. At this point the reaction mass bonyllfl'hydl'oxythloformlmldateObtalned- It 15 is cookd to c. and 547 parts of the product methylcrystallized from benzenecyclohexane to give pure mate- O 1 (carbamoyl)N (methylcarbamoyloxy)thioformmeltmg P 53-55 imldate 1s ijlltered off.The product has a melting point 00 EXAMPLE IV of l6ll65 C.

The compounds of Table II are prepared by the pro- To a solution of164.6 parts of distilled ethyl 2-chlorocedures of Examples I and II,using the mercaprans and acetoacetate in 394 parts of ethanol is addedat 5 C. isocyanates listed in place of methyl mercaptan and over onehour 77 parts of ethyl nitrite, prepared as demethyl isocyanate ofExamples I and II. scribed in Example I. The reaction mixture is stirredat TABLE TI Mereaptan Isocyanate Product Ethyl mereaptan Methylisoeyanate Ethyl lcal'ltumoyl-N-(methylcarbamoyloxy)- thioformimidate.

Allyl mereaptan do Allyl l-carbmnoyhN-(methylcarban10yloxy)-thioforminlidate.

But-Z-cnyl ruercaptan Ethyl isocyauatcBut-2-enyl1-carban10yLN-(0thylcarbamoylexy)- thiolorininiidate.

l'sopropylmercaptan Allyl isocyanate lsopropyll-earbaInoyl-N-(allylcarbamoyloxy)- thioforiniidate.

Methyl mercaptan Iropnrgyl isocyanate Methyl l-carmmoyl-N-(propargylcarbamoyloxy)- thioformimitlate.

Propylmercaptan Methyl isocyanatePropyll-carbamoyl-N-(methylcarbamoyloxy)- thioformimldate.

Allyl mereaptan Allyl isocyanate Allyll-carbamoyI-N-(allylcarbamoyl0xy)- thioformirnidatc.

lsopropyl mercaptan Methyl isoeynnateIsopropyl1-carbamoyl-N-(methylcarbamoyloxy)- thioformirnidate.

Butylmereaptan .do Buty l-carl)alnoyl-N-(methylearbamoyloxy)-thiolormimidate.

sec-Butyl mercaptan d0 sec-Bntyl l-carbarnoyl-N(methylearbamoyloxy)thioformimldate.

tert-Butyl mercaptan Methyl isocyanate tert-Butyll-earbamoyl-N-(methylearbamoyl- 0xy)thiolormimidate.

Methyl mercaptan Ethyl isocyanate Methyll-carbamoyLN-(ethylearbamoyloxy)- thioformimidate.

Butyl mereaptanuu; .410 Butyl l-carbarnoyl-N-(ethy1carbamoyl0xy)-thiolormimidate.

Methyl mercaptan Isopropyl isoeyanateMethyl1earbamoyl-N-(isopropylearbamoyloxy)- thioformimidate.

Butyl mcrcaptan d0 Butyl l-carbamoyl-N-(isopropylcarbamoyloxy)-thiotormimidate.

Allyl mercaptan d0 Allyl Lcarbarnoyl-N-(isopropylcarbamoyloxy)thioformimidate.

Do Propyl isoeyanate Allyl l-earbamoyl-N-(propylcarbamoyloxy)-thiol'ormimidate.

Methyl mercztptan Allyl isocyannte Methyll-carbamoyl-N-(allylcarbamoyloxy)- thiol'ormirnidate.

Butylmercaptan du Butyl l-carbamoyl-N-(allylcarbamoyloxy)-thioformimidate.

Allyl mercaptan Propargyl isocyanate Allyll-carbamoyl-N-(propargylearbamoyloxy)- thiolorrnimidate.

10 C. for a further four hours at 5 C., and is then al- (b) reacting theproduct of step (a) with an alkyl nitrite lowed to rise to ambienttemperature. The solvent is in the presence of hydrogen chloride and inthe evaporated at reduced pressure. The crystalline residue presence ofwater, methanol, ethanol, isopropanol (150 parts) is then slurried with118 parts of cyclohexane, or their mixtures, at a temperature between-20 C. and the crystals filtered off, washed with a further 40 r and 50C. parts of cyclohexane and dried to give 126 parts of rela- (c) mixingthe product of step (b) with an alkyl mertively pure 1(ethoxycarbonyl)formhydroxamoyl chlocaptan of the formula ride meltingat 6878 C. Recrystallization from benzene gives material melting at79-80.5 C. l

EXAMPLE V wherein R is as defined above; and then raising the To aStirred Suspension of 48 Parts of 50% Sodium ypH to the range of 5-9 bythe addition of a hydroxide dride and mineral oil in 648 parts oftetrahydrofuran is carbonate or bi b of di potassium, laddedportion-wise over a one-hour period 114 parts of i or magnesium;

methyl 1 (carbamoyl)-N-hydroxythioformimidate. The

(d) aminating the product of step (c) with about 2 temperature ismaintained at to C. After subsidence moles per mole of product ofammonia, a primary of hydrogen evolution, 107.5 parts ofdimethylcarbamoyl amine or a secondary amine in the presence of water,chloride is added dropwise at 15-25 C. Stirring is conmethanol, ethanol,isopropanol or their mixtures; tinued for one hour after the completionof the addition. and The inorganic solids are then removed by filtrationand 20 (e) reacting the product of (d) with either the methyll-carbamoyl-N-(dlmethylcarbamoyloxy)thio- -(1) a carbamoyl chloride inthe presence of a formimidate is recovered by removal of the solventunder base; or reduced pressure. (2) an isocyanate in the presence orabsence of a The compounds of Table III are prepared according to basiccatalyst; in Water, acetone, methylene chlothe procedures of Example V,using the N-hydroxythio- 25 ride, methyl ethyl ketone or methyl isobutylformimidates and carbamoyl chlorides listed in place of ketone. methyll-(carbamoyl)-N-hydroxyth1oformimidate and di- 2. The process of claim 1wherein the amination is carmethylcarbamoyl chloride. ried out withammonia.

TABLE III N-hydroxythioiormimidate Carbamoyl chloride Product Methyl1-carbamoyl-N-hydroxythioformimidate N-allyl-N-methylearbamoyl chlorideMethyl l-carbamoyl-N-(N-allyl-N-methylcarbamoyloxy)thioformi midate. DoN-metl}yl-N-propargylcarbamoyl Methyll-carbamoyl-N-(N-methyl-N-propargylcarbachloride.moyloxy)thioformimidate. N -metl 1y1-N-propylcarbamoyl Methyll-carbamoyl-N- (N-methyl-N-propylcarbamoylhloride. oxy)thioformimidate.D0 N-ethyl-N-methylcarbamoylchlorideMethylfi-earbamoyg-N-(N-ethyl-N-methylcarbamoyl- I oxy t io ormimi ate.Methyl l-methylcarbamoyl-Nhydroxythlo- Dlmethylcarbamoyl chloride Methyl1- (methylcarbamoyd) -N-dimethylcarbamoylformimiclate.0xy)thi0formimidate. Methyl 1- d1methylcarbtunoyl-N-hydroxythlod0 Methyll-(dimethylearbamoyD-N-(dimethylcarbamoylformirnldate.oxy)thioiormi.rnidate. Methyl 1- cyclopentylcarbamoyl-N-hydroxyt o- -d0Methyl l-(cyelopentylcarbamoyl)-N-(dimethylcarbamoylformnnldate.0xy)thioiorm'nnidate. Propyl l-carbamoyl-N-hydroxythlofolmlmldate- -d0Prfopyl l-carbamoyl-N-(dimethylcarbamoyloxy)thio- OI'lIllml a Ethyl1-carbamoyl-N-hydroxyt ioformim date d0 Etlz hyll-cabamoyl-N-(dimethylcarbamoyloxy)-thio- OImlml a E- Butyll-carbamoyl-N-hydroxythiOIOI'mimida Q d0 Blflliyll-cabtamoyl-N-(dimethylearbamoyloxy)-thio- 0111111131 8. e. Methyll-piperidinocarbonyl-N-hydroxyt io- Methyll-piperidinocarbonyl-N-(dimethylearbamoyliormimidate.oxy)thiofonnimidate. Allyl lcarbamoyl-N-hydroxy- 0 Allyl 1-earbamoyl-N-(dimethylcarbamoyloxy) thiothroformimldate formimidate. But- 2-enyl1-carbam0ylN-hydr0Xyth10f0 m m 0 But-2-enyll-carbamoyl-N-(dimethylcarbamoyl0xy)- nndate. thioformimidate.

I claim: 3. The process of claim 1 wherein amination is carried 1. Aprocess for preparing alkyl l-(carbamoy1)-N-(carout with dimethylamine.bamoyloxy)thioformimidates 0f the f r ula 4. The process of claim 1wherein step (a) is carried out R in Water, using elemental chlorine asthe chlorinatin (1) i i 4 t O N-e-o=N-o-ri-N acen 5. The process ofclaim 1 wherein step (a) is carried R2 R1 5 out in the absence ofsolvent using sulfuryl chloride as h i the chlorinating agent. R isalkyl of 1 through 4 carbon atoms or alkenyl of 3 6. The process ofclaim 1 wherein step (b) is carried through 4 carbon atoms; u in l- R ishydrogen, alkyl of 1 through4 carbon atoms, alkenyl 7. The process ofclaim 1 wherein step (c) is carried of 3 through 4 carbon atoms,rnethoxy or cycloalkyl of out after cooling to a temperature below 20 C.3 through 5 carbon atoms; 8. The process of claim 1 wherein step (d) iscarried 3 18 hydrogen, alkyl 0f 1 through 4 Carbon atoms, or out inmethanol, ethanol, isopropanol or their mixtures alkenyl of 3 through 4carbon atoms; with the prowith Water viso that R and R can be takentogether and are alkylene of 2 through 6 carbon atoms, and with thelimitation that R and R never total more than 7 carbon 9. The process ofclaim 1 wherein excess ammonia or amine are removed after step (d) andprior to step (e). 10. The process of claim 1 wherein step (e) iscarried atoms; R glkyl of 1 through 3 carbon atoms, allyl or propargyl;g ijz gg gs i igf gg or methyl R5 is hydrogen or methyl; 11. The processof dam 1 wherein step (e) is carr1ed b h Steps comprising out us1ng acarbamoyl chlorlde and triethylamine, tri- (a) chlorinating methyl,ethyl, or isopropyl acetoacetate methylamme, or a hydroxide, carbonateor bicarbonate of in the presence or absence of water, methanol,ethanol, Sodlllm, Potasslum, calclllm 0f magnfislum as e.

isopropanol or their mixtures at a temperature be- The Process of 61mm 1Whfifeln p 15 carfld tween 0 C. and 70 C.; out in the absence of asolvent and steps (b), (c) and (d) 1 1 are operatively combined inwater, methanol, ethanol, isopropanol or their mixtures.

13. A process for preparing hydroxamoyl chlorides of the formula lt0CCCl wherein R is methyl, ethyl or isopropyl by the steps comprising (a)chlorinating methyl, ethyl or isopropyl acetoacetate in the presence orabsence of water, methanol, ethanol, isopropanol or their mixtures at atemperature between 0 C. and 70 (3.;

(b) reacting the product of step (a) with an alkyl nitrite in thepresence of hydrogen chloride and in the presence of water, methanol,ethanol, isopropanol or their mixtures, at a temperature between 20 C.and 50 C.

14. The process of claim 13 wherein step (a) is carried out in water,using elemental chlorine as the chlorinating agent.

15. The process of claim 13 wherein step (a) is carried out in theabsence of a solvent using sulfuryl chloride as the chlorinating agent.

16. The process of claim 13 wherein step (b) is carried out in ethanol.

17. A process for nitrosating alkylesters of Z-chloroacetoacetates ofthetformula v References Cited UNITED STATES PATENTS 3,256,330 6/1966Kilsheimer et al. 260 566A HENRY R. JI'LES, Primary Examiner S. D.WINTERS, Assistant Examiner US. Cl. X.R.

